Rebooting the brain: Preventing neurological damage in newborns

Kristin Smith thought she was in labor. It was her second pregnancy; she knew the drill. After an exam at the hospital, however, medical professionals told her she wasn’t ready to be admitted.

“They gave me Ambien [a hypnotic sedative, intended to aid sleep] and sent me home,” she says. “I’ve done some research; it is fairly common when someone’s not in labor and they think they are. They send them home to relax and let them sleep through it.”

Kristin took one of the two pills. Then she and her husband went home. But they quickly turned around.

“I knew I was in labor,” Kristin says. “There was no doubt in my mind.”

Soon, Kristin delivered a healthy daughter, Madigan, nicknamed Maggie. “I had her two hours after being told I wasn’t in labor,” Kristin says.

Maggie’s Apgar scores were high, and she was thriving shortly after delivery. Nurses initiated skin-to-skin contact between mother and baby. Maggie began to nurse. By then, Kristin believes, the Ambien may have fully kicked in—and the labor and delivery staff were unaware that their patient was under the influence of the drug.

“I was totally out of it,” Kristin recalls. “I think I appeared conscious and lucid but I really wasn’t.” The nurses turned out the lights in the room and left mother and baby to bond. Maggie fell asleep while nursing; Kristen also fell asleep.

A nurse returned to the room and quickly realized that baby Maggie, pressed against Kristin as she nursed, had stopped breathing. “I just remember the nurse saying ‘Oh, my God!’ and she pulled her off my chest,” says Kristin. “She was completely gray.” Medical personnel filled the room and desperately began working to resuscitate her newborn.

No one expects the labor and delivery experience to shift from joyful anticipation to medical crisis. But it can.

When a newborn suffers from a lack of oxygen during the birth process, for any reason, acute neurologic injury can be the result. Damage to the brain is devastating; it can steal away the hope that a child will be able to reach his or her full mental and physical potential.

Experts call it hypoxic-ischemic encephalopathy (HIE). According to United Cerebral Palsy (UCP), one of the largest non-profits to provide services to disabled children and adults, HIE affects approximately two to three cases per 1,000 full-term live births and can lead to devastating disabilities, or even death.

Despite advancements in neonatal intensive care, the outcome for infants with HIE remains poor. Ten to 15 percent of infants with HIE die shortly after birth. Approximately 25 percent of those who survive will suffer permanent neurological damage such as mental retardation, cerebral palsy or seizures.

But there’s glimmer of hope for babies affected by HIE because of a cooling treatment only recently pioneered by a handful of neonatologists, including Phoenix Children’s Hospital’s Cristina Carballo, M.D. With some luck, timing and a centuries-old concept, the newborn brain can actually re-boot—often with few or no lasting effects from the oxygen deprivation that occurred.

“We’ve seen EEGs go from abnormal to normal. We’ve seen the MRIs go from abnormal to normal,” says Carballo, who directs the Neuro-NICU at PCH. “It’s incredible.”

Amy Torgersen and son Joaquin Ramos. Photo by Daniel Friedman.

Labor for Amy Torgersen was going well until it was time for her to deliver her son. Joaquin Ramos was born full term, and two pounds heavier than her first two children. Amy recalls enduring an exceptionally long pushing phase. When Joaquin finally emerged, he had no vital signs. Amy heard the words “code teddy bear”—used in some hospitals to indicate cardiac arrest in a child—over the loudspeakers. Suddenly, the room was filled with medical professionals.

Five, then 10 minutes went by as the team continued chest compressions and “bagging,” or gently squeezing oxygen through a tube that had been placed into Joaquin’s airway. “It was just a whirlwind of activity,” says Amy. “I noticed the scurry in the back of the room but it took me a few minutes to realize that there was something wrong with the baby.”

One of the doctors happened to have heard about Carballo’s cooling treatment program at PCH. After Joaquin was stabilized, he was flown there by helicopter.

“He had weak vitals. I was able to touch him before he left, but not hold him,” says Amy. “And I’ll never forget, when I touched him, he turned and looked at me. We were very surprised that he was responsive. They told me not to touch him, because they didn’t want him to be stimulated. I don’t know if ‘brain dead’ is the right term, but there was that possibility.”

Joaquin Ramos in his Cool-Cap. Photo courtesy of the family.

Therapeutic hypothermia, or the process of lowering a patient’s body temperature to preserve brain function, dates back centuries. In ancient times, the Greek physician Hippocrates favored packing wounded soldiers in ice and snow. More recently, during the 1950s, doctors pioneered the cooling of adult cardiac patients during surgery. And there are the miraculous stories of drowning victims—pulled out of very cold waters after many minutes—who are resuscitated and restored to health.

Researchers began looking at using cooling therapies on newborns in the early 2000s, says Carballo, who notes that attempting new treatments on neonates tends to lag behind that of other populations. “Potential outcomes could be detrimental instead of helpful, and neonates tend to get the last of the technology partly for that reason.” Carballo became interested in piloting a program at PCH around 2005. By 2008 she had treated her first HIE baby with a device called a Cool-Cap.

When brain cells lose oxygen, they start to die. As they do, the cells emit a chemical that can harm other cells around them. However, recent discoveries show that that severe hypoxia-ischemia may not necessarily cause immediate cell death, as was previously thought. Instead, a complex biochemical series of events takes place over time. That is what ultimately leads to neuronal loss.

For newborns, experts are finding that a brief window exists during which this process can be reversed. The infant brain has tremendous plasticity, much more so than an adult brain, says Carballo. Lowering the baby’s core temperature from a normal 98.6 to around 92 degrees and lowering the midbrain’s temperature to 82.4 degrees for about 72 hours appears to be the equivalent of pressing a re-set button. “Everything quiets down, and those cells have a chance to recover,” says Carballo. “They don’t produce the chemicals that harm other parts of the brain and end up leading to the devastating cerebral palsy we see in these kids.”

Carballo’s team was the first in Arizona to treat babies with the cooling method, beginning with the Cool-Cap. As they honed the treatment, they shifted from the cap to a blue, liquid-filled blanket placed underneath the entire length of the baby. The blanket connects to a machine that circulates refrigerant. A special thermometer is placed midway through the baby’s esophagus and constantly measures the core body temperature. Doctors administer medications to minimize any discomfort.

As the cooling takes place, the baby’s brain is carefully monitored by the PCH epilepsy unit. Seizures, if left untreated, could be detrimental. Bedside management throughout the process is aggressive, says Carballo. Critical care pediatric neurologists devise the treatment plan, and pediatric neuro-radiologists read MRIs performed by equipment specifically designed for tiny infants.

The cooling treatment may be the foundation of the Neuro-NICU, but it is Carballo’s hope that the concept of neuro-monitoring might help any baby who is neurologically affected at birth. “A baby who starts having seizures in the first couple of days of life, a baby whose neuromuscular tone doesn’t look right, a baby whose brain we know has a malformation” stands to benefit from the resources her team has put together, she says. “We’re not just a cooling center. Our goal is to optimize neuro-developmental outcome in all babies affected neurologically.”

Multiple causes lie behind HIE. Suffocation incidents, like what happened to Kristin and Maggie Smith, aren’t typical. Uterine rupture, infection, cord accidents (where the cord slips out before the baby is delivered) or placental abruption (where the placenta starts separating from the uterus before the baby comes out) are among the most common, according to Carballo. Doctors indicated that shoulder dystocia, a situation where the baby’s shoulder gets “stuck” in the birth canal, could have been the reason that Joaquin Ramos suffered a pulmonary hemorrhage at birth, causing his HIE, says Amy Torgerson.

The window to begin cooling the brain is short, and the availability of the procedure itself is so new that there is no guarantee a baby who could benefit will undergo this treatment. Doctors, nurses and parents are slowly becoming aware of the options, but as with any new development in medicine, spreading the word takes time. Some babies have been transported to PCH because of pure luck—someone involved in the baby’s care had heard of Carballo’s research and the Neuro-NICU. But in the Maize family’s case, it was a determined dad with an inexplicable instinct.

Jennifer Maize had been in labor all day, and monitors were beginning to show that her baby was in distress. Doctors could see his head in the birth canal, but they were unable to tell if the baby was face down or face up. A face-up delivery can be tough, sometimes making it harder for a baby to clear the mother’s pelvis. “No matter how hard I pushed, he wasn’t going anywhere,” Jennifer remembers. After three hours of pushing, she underwent an emergency cesarean section under general anesthesia.

Steve Maize had never witnessed a C-section before; the couple’s daughter, Avery, now 5, was delivered vaginally. He stood near Jen’s shoulder awaiting the birth of his son. Although it seemed like an eternity, says Steve, things seemed to be progressing routinely—until Drew Tillman Maize, 8 lbs., 8 oz., emerged. “Once they got Drew out, there was a mad rush. I remember them shouting out ‘code teddy bear.’ I’m not a doctor, but I knew that couldn’t be a good thing.”

When Steve got a first glance at his son, he was blue and lifeless. “There were so many people in the room, I was just pinned in the corner with no other option but to watch. It was a solid two and a half minutes where he didn’t have a pulse, he didn’t have oxygen. There’s a sense of helplessness,” he says. “You are excited, but on the flip side you see a life that may not get a chance.”

There was no way at that time to tell how this difficult birth, and the lack of oxygen, would affect Drew’s health. Initially, says Steve, doctors suggested moving Drew to an ICU at a local regional hospital for care. But that didn’t feel right to Steve: “I was adamant about other options.” At that point, says Steve, a hospital staff member suggested PCH. Drew was evacuated by air and received by Carballo and her team. They began preparing Drew for the cooling treatment.

Before a baby is moved to the PCH program, certain criteria must be met. Apgar scores, blood tests, neurological state at the time—these factors determine whether hypothermia therapy can help. Once at PCH, babies receive further neurological testing, including an electroencephalogram (EEG), to determine the level of encephalopathy, or inflammation of the brain. A moderate or severe range qualifies them to be cooled. From the time of birth, or injury, there are only about six hours to begin the therapy, says Carballo. “It’s not a lot of time.”

If a baby is born outside of the Valley, transport may push the six-hour limit. Carballo says many medical facilities have the means to begin lowering the body temperature. “If you’re in Show Low, and it’s winter and there is a snowstorm, they can start passively cooling the baby, and wait for the transport. We count that as part of the cooling.” When the baby arrives at PCH, intensive monitoring can begin.

Steve and Drew Maize during swim lessons. Photo by Daniel Friedman.

When Jennifer woke up in the recovery room, Steve and baby Drew were gone. A nurse and a close friend broke the news to Jen. “I was confused because my friend wasn’t there before, only Steve. She had to explain that Drew was born with no vital signs.” Jennifer became extremely ill with a bowel obstruction, which lengthened her hospital stay. “I didn’t get to see Drew for eight days, until I was released. It was very, very traumatic. It was so hard to be in that hospital room on a post-partum floor, hearing all of the babies crying next door.”

As of mid-July 2012, Carballo and her team have treated 129 babies with hypothermia therapy. What she has found so far is striking. Out of 52 treated babies for whom she has complete follow-up data, 37 had moderate encephalopathy. Of those, 35 are now normal. For the 15 babies classified as severe, 14 are now normal.

Typically, for babies initially assessed with moderate encephalopathy, 30 percent will develop cerebral palsy. But of the moderate cases treated in Carballo’s group, only six percent had a cerebral palsy outcome. The result for babies assessed as severe is even more striking. Of babies initially assessed with severe encephalopathy, 90 percent typically will develop cerebral palsy. For the babies who were treated with hypothermia therapy, the rate was just one percent.
It’s nothing short of remarkable, says Carballo, who took an interest in children with disabilities when, as a high school student, she’d help her mother, a special education teacher, in the classroom. Curiosity about the “whys” behind each child’s challenges led Carballo, long before today’s HIPAA regulations, to take a peek at the records. “I’d look through the charts to see what caused this baby to be disabled, what happened. That’s what led me into medicine, into neonatology. I’ve been pushed by a higher source and finally got to this point.”

Her interests led to an eventual board position for United Cerebral Palsy of Central Arizona, and involvement in advocating for children with disabilities. Armando Contreras, chief executive officer of the organization, hopes to support Carballo in raising awareness of these new discoveries. “We want to get the word out not only here in the state, but also throughout the nation and perhaps globally at some point, to let folks know what this cooling process is,” he says. Adds Carballo, “There are babies being missed out there because the people aren’t picking up on it. It can really make a difference in the long-term life of a child, and parents have every right to request it.”

Maggie Smith was the 17th of the 129 babies to be cooled. Her encephalopathy fell into the moderate range, giving her a 30 percent chance of developing cerebral palsy.

“The first year was a little rough, says Kristin, “just because we didn’t know.” During that time, a variety of specialists monitored Maggie’s growth and development—physical therapists, speech therapists, a psychiatrist. Now, at age 3, she has no trace of delay whatsoever. Without the cooling treatment, “we would have a very different child,” Kristin says. “It is a miracle, absolutely.”

Joaquin Ramos was 30th of the 129, and in the severe group. He’s the only baby so far that was simultaneously cooled while supported by extracorporeal membrane oxygenation (ECMO)—a device used for seriously ill infants similar to the heart-lung bypass machines used in open-heart surgeries. “It’s a dubious distinction,” says Amy, who adds that, at almost 3, Joaquin has no developmental delays, no hearing or vision loss and no cerebral palsy. “It’s pretty miraculous that he did as well as he did.”

Drew Maize on a cooling blanket. Photo courtesy of the family.

Jennifer Maize describes Drew Tillman Maize, now 2, as a happy boy with a streak of mischief. Like his namesake, she says, Drew is strong, determined, and “what he wants, he’s going to get.” Drew fell into the severe category when he was assessed at PCH, and was the 57th baby to be cooled.

Because of his birth, he qualified for early intervention services, says Jen. That provided a wealth of resources, including some speech therapy. He’s grown out of the need for that, however, and so far seems just fine. “His development seems to be on par with your average 2-year-old,” says Steve. “He’s absolutely fearless, and goes 100 miles an hour. If you saw him, or met him, you’d never in a million years guess what he’s been through. He’s a fighter.”

Unanswered questions surrounding the cause, and the ultimate outcome, of Drew’s HIE remain, says Steve. “I wouldn’t say he’s out of the woods yet, but for now, Drew’s healthy, and he’ll have a story to tell when he gets older. But I truly believe if we had gone anywhere else, and had not gotten the cooling therapy, the interview we’re doing today would be totally different. For as sad of a situation that we were in, we truly were in the right place at the right time.”

EDITOR’S NOTE: This story won first-place honors in the health reporting category at the 2012 Arizona Press Club Awards.

5 Responses

This is such a beautifully written article. The cooling blanket also saved my husband’s life nearly 9 months ago when he suffered a massive heart attack. He recovered completely with no brain damage. Thank you to the many doctors, including Dr. Carballo, who are always looking for new ways to save lives.

Clearly a deeply researched article, wonderfully written. Vicki, I’m sure this life-saving information will have a positive ripple effect as it spreads in print and online. Thanks so much for work well done.

This is a very clearly written informative article that everyone should read especially if you are having a child. I appreciate the detailed research and easy to understand explanations. I will pass this on to my daughter and her friends who are beginning to start their families.

My baby was a candidate for the cooling blanket and although it was hard to see her there and not hold her for days, I thank God for people like Carballo who are truly working miracles. My daughter is only 3 months old now so time will still have to tell but she seems to be doing wonderfully now. Guardian angels were watching over here and I am so grateful for the cooling protocol.

My daughter was put on a cooling blanket after her accident and I hated that thing, didn’t understand how it’d help. Reading all this gives me even more hope and faith in her recovery. I never would have thought it could be of so much benefit for her. It’s only been a little over a month since her accident so we still have a LOOOONG road of recovery but I have faith. She suffered severe brain damage and the doctors have been very blunt and straight forward. They said she would never wake up and if she did she’d never move. Well she’s woken up, and she moves. Not like she normally would but two things they said she would never do, and that was IF she lived they said, she has done. Thank you all for your stories. It helps.

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